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Gene Review

Gls  -  glutaminase

Rattus norvegicus

Synonyms: GLS, Glut, Glutaminase kidney isoform, mitochondrial, K-glutaminase, L-glutamine amidohydrolase, ...
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Disease relevance of Gls

  • Thus AUF1 may mediate the rapid turnover of the GA mRNA, whereas increased binding of zeta-crystallin during acidosis may inhibit degradation and result in selective stabilization [1].
  • Biosynthesis and processing of mitochondrial glutaminase in HTC hepatoma cells [2].
  • Partial proteolysis of the fusion protein produced by a lysogen of the isolated phage generated a series of immunoreactive peptides that co-migrated with those derived from the purified brain glutaminase [3].
  • (a) Presence of a prominent glutaminase activity in erythroleukemia and chloroma mitochondria is evidenced by their active glutamine-supported respiratory state 3 [4].
  • Chemically-induced acidosis and alkalosis decreased (46%, p less than 0.001) and increased (24%, p less than 0.001), respectively, the activity of intestinal glutaminase, but had no effect on the colonic enzyme [5].

Psychiatry related information on Gls


High impact information on Gls

  • This study characterizes the rat ovary as a site of hormonally dependent glucose transporter (Glut) expression, and explores the potential role of interleukin (IL)-1, a putative intermediary in the ovulatory process, in this regard [7].
  • Intravenously fed rats showed a simultaneous increase in glutamine utilization and a decrease in glucose utilization compared with intragastrically fed and control rats, without parallel changes in glutaminase and hexokinase activities [8].
  • In contrast, glutamine use rate was 45% higher, and this was correlated with a higher maximum velocity of glutaminase in these cells [9].
  • The gene coding for carbamoyl-phosphate synthetase I was formed by fusion of an ancestral glutaminase gene and a synthetase gene [10].
  • In the mammalian enzyme, however, the glutaminase domain lacks a cysteine residue previously shown to interact with glutamine [10].

Chemical compound and disease context of Gls


Biological context of Gls


Anatomical context of Gls


Associations of Gls with chemical compounds

  • A tetracycline-responsive promoter system was developed in LLC-PK(1)-F(+) cells to perform pulse-chase analysis of the turnover of a chimeric beta-globin (betaG) mRNA that contains 960 bp of the 3'-UTR of GA mRNA including the pH-RE [1].
  • Inhibition of glutaminase reduced glutamate staining [23].
  • The rate of urea production from glutamine (1 mmol/L or 10 mmol/L) in HX rats was significantly lower than that of SO rats with a concomitant decrease in hepatic glutaminase activities [24].
  • Again, most dopamine neurons immunostained for glutamate; they were also immunoreactive for phosphate-activated glutaminase, the major source of neurotransmitter glutamate [23].
  • Glutamate formed from glutamine by phosphate-dependent glutaminase undergoes quantitative transamination by aerobic tumor mitochondria to yield aspartate [25].

Regulatory relationships of Gls

  • Significant proportions of Calb(+) (>40%) and Calret(+) (>80%) neurons were immunopositive for phosphate-activated glutaminase, the synthetic enzyme for transmitter glutamate [26].
  • Administration of nerve growth factor, brain-derived neurotrophic factor and insulin-like growth factor-II protects phosphate-activated glutaminase in the ischemic and reperfused rat retinas [27].
  • During CMA, SN1 expression increases five- to six-fold and appears also in cortical tubule cells in parallel with the increased expression and activity of phosphate-activated glutaminase, a mitochondrial enzyme involved in ammoniagenesis [28].
  • Virtually all Nurr1-expressing neurons exhibit immunoreactivity for phosphate-activated glutaminase but not for gamma-aminobutyric acid, suggesting that they are glutamatergic-excitatory neurons [29].
  • This increase in glutaminase was completely blocked by the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid, and by the NMDA receptor-linked Ca2+ ion channel blockers, MK 801 and Mg2+ [30].

Other interactions of Gls

  • RNase H cleavage and Northern blot analysis of the 3'-ends established that rapid deadenylation occurred concomitantly with the rapid decay of the betaG-GA mRNA in cells grown in normal medium [1].
  • The specific stimulation of NMDA receptors in PKC-depleted granule neurons or in the presence of reasonably specific PKC inhibitors also produced significant elevation in the activity of glutaminase and the expression of c-fos protein [31].
  • Liver glutamine synthase activity increased by 58% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected [32].
  • Arginase activity was not affected, whereas glutaminase activity was enhanced by 50% [16].
  • It is suggested that, in isolated hepatocytes, BCH-induced stimulation of glucose and urea formation from glutamine results from activation of glutaminase by a mechanism which is distinct from that of glucagon [33].

Analytical, diagnostic and therapeutic context of Gls


  1. Role of deadenylation and AUF1 binding in the pH-responsive stabilization of glutaminase mRNA. Schroeder, J.M., Ibrahim, H., Taylor, L., Curthoys, N.P. Am. J. Physiol. Renal Physiol. (2006) [Pubmed]
  2. Biosynthesis and processing of mitochondrial glutaminase in HTC hepatoma cells. Perera, S.Y., Voith, D.M., Curthoys, N.P. Biochem. J. (1991) [Pubmed]
  3. Isolation of a cDNA for rat brain glutaminase. Banner, C., Hwang, J.J., Shapiro, R.A., Wenthold, R.J., Nakatani, Y., Lampel, K.A., Thomas, J.W., Huie, D., Curthoys, N.P. Brain Res. (1988) [Pubmed]
  4. Prominent glutamine oxidation activity in mitochondria of hematopoietic tumors. Abou-Khalil, W.H., Yunis, A.A., Abou-Khalil, S. Cancer Res. (1983) [Pubmed]
  5. The maximal activity of phosphate-dependent glutaminase and glutamine metabolism in the colon and the small intestine of streptozotocin-diabetic rats. Ardawi, M.S. Diabetologia (1987) [Pubmed]
  6. Loss of glutaminase-positive cortical neurons in Alzheimer's disease. Akiyama, H., McGeer, P.L., Itagaki, S., McGeer, E.G., Kaneko, T. Neurochem. Res. (1989) [Pubmed]
  7. The midcycle increase in ovarian glucose uptake is associated with enhanced expression of glucose transporter 3. Possible role for interleukin-1, a putative intermediary in the ovulatory process. Kol, S., Ben-Shlomo, I., Ruutiainen, K., Ando, M., Davies-Hill, T.M., Rohan, R.M., Simpson, I.A., Adashi, E.Y. J. Clin. Invest. (1997) [Pubmed]
  8. Parenteral nutrition modifies glucose and glutamine metabolism in rat isolated enterocytes. Colomb, V., Darcy-Vrillon, B., Jobert, A., Guihot, G., Morel, M.T., Corriol, O., Ricour, C., Duée, P.H. Gastroenterology (1997) [Pubmed]
  9. Effect of germfree state on the capacities of isolated rat colonocytes to metabolize n-butyrate, glucose, and glutamine. Cherbuy, C., Darcy-Vrillon, B., Morel, M.T., Pégorier, J.P., Duée, P.H. Gastroenterology (1995) [Pubmed]
  10. The gene coding for carbamoyl-phosphate synthetase I was formed by fusion of an ancestral glutaminase gene and a synthetase gene. Nyunoya, H., Broglie, K.E., Lusty, C.J. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  11. Adaptive alterations in cellular metabolism with malignant transformation. Fischer, C.P., Bode, B.P., Souba, W.W. Ann. Surg. (1998) [Pubmed]
  12. Modulation of cellular proliferation alters glutamine transport and metabolism in human hepatoma cells. Bode, B.P., Souba, W.W. Ann. Surg. (1994) [Pubmed]
  13. The regulation of phosphate-activated glutaminase activity and glutamine metabolism in the streptozotocin-diabetic rat. Watford, M., Smith, E.M., Erbelding, E.J. Biochem. J. (1984) [Pubmed]
  14. In vivo release of glutamate in nucleus tractus solitarii of the rat during hypoxia. Mizusawa, A., Ogawa, H., Kikuchi, Y., Hida, W., Kurosawa, H., Okabe, S., Takishima, T., Shirato, K. J. Physiol. (Lond.) (1994) [Pubmed]
  15. Antisense glutaminase inhibition decreases glutathione antioxidant capacity and increases apoptosis in Ehrlich ascitic tumour cells. Lora, J., Alonso, F.J., Segura, J.A., Lobo, C., Márquez, J., Matés, J.M. Eur. J. Biochem. (2004) [Pubmed]
  16. Changes in distribution and activity of glutamine synthetase in carbon tetrachloride-induced cirrhosis in the rat: potential role in hyperammonemia. Gebhardt, R., Reichen, J. Hepatology (1994) [Pubmed]
  17. Effect of acute alterations in acid-base balance on rat renal glutaminase and phosphoenolpyruvate carboxykinase gene expression. Hwang, J.J., Curthoys, N.P. J. Biol. Chem. (1991) [Pubmed]
  18. Isolation, characterization, and in vitro expression of a cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase. Shapiro, R.A., Farrell, L., Srinivasan, M., Curthoys, N.P. J. Biol. Chem. (1991) [Pubmed]
  19. Expression of mitochondrial HMGCoA synthase and glutaminase in the colonic mucosa is modulated by bacterial species. Cherbuy, C., Andrieux, C., Honvo-Houeto, E., Thomas, M., Ide, C., Druesne, N., Chaumontet, C., Darcy-Vrillon, B., Duée, P.H. Eur. J. Biochem. (2004) [Pubmed]
  20. Glutaminase-positive and glutaminase-negative pyramidal cells in layer VI of the primary motor and somatosensory cortices: a combined analysis by intracellular staining and immunocytochemistry in the rat. Kaneko, T., Kang, Y., Mizuno, N. J. Neurosci. (1995) [Pubmed]
  21. Localization of glutaminase-like and aspartate aminotransferase-like immunoreactivity in neurons of cerebral neocortex. Donoghue, J.P., Wenthold, R.J., Altschuler, R.A. J. Neurosci. (1985) [Pubmed]
  22. Expression and role of ionotropic glutamate receptors in pancreatic islet cells. Inagaki, N., Kuromi, H., Gonoi, T., Okamoto, Y., Ishida, H., Seino, Y., Kaneko, T., Iwanaga, T., Seino, S. FASEB J. (1995) [Pubmed]
  23. Dopamine neurons make glutamatergic synapses in vitro. Sulzer, D., Joyce, M.P., Lin, L., Geldwert, D., Haber, S.N., Hattori, T., Rayport, S. J. Neurosci. (1998) [Pubmed]
  24. Decreased ureagenesis from alanine, but not from ammonia and glutamine, in the perfused rat liver after partial hepatectomy. Moriyama, M., Makiyama, I., Shiota, M., Uesugi, K., Kannan, Y., Ohta, M., Kimura, K., Sugano, T. Hepatology (1996) [Pubmed]
  25. The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme. Moreadith, R.W., Lehninger, A.L. J. Biol. Chem. (1984) [Pubmed]
  26. Parvalbumin, calbindin, or calretinin in cortically projecting and GABAergic, cholinergic, or glutamatergic basal forebrain neurons of the rat. Gritti, I., Manns, I.D., Mainville, L., Jones, B.E. J. Comp. Neurol. (2003) [Pubmed]
  27. Administration of nerve growth factor, brain-derived neurotrophic factor and insulin-like growth factor-II protects phosphate-activated glutaminase in the ischemic and reperfused rat retinas. Tomita, H., Ishiguro, S., Abe, T., Tamai, M. Tohoku J. Exp. Med. (1999) [Pubmed]
  28. Induction and targeting of the glutamine transporter SN1 to the basolateral membranes of cortical kidney tubule cells during chronic metabolic acidosis suggest a role in pH regulation. Solbu, T.T., Boulland, J.L., Zahid, W., Lyamouri Bredahl, M.K., Amiry-Moghaddam, M., Storm-Mathisen, J., Roberg, B.A., Chaudhry, F.A. J. Am. Soc. Nephrol. (2005) [Pubmed]
  29. Organization and development of corticocortical associative neurons expressing the orphan nuclear receptor Nurr1. Arimatsu, Y., Ishida, M., Kaneko, T., Ichinose, S., Omori, A. J. Comp. Neurol. (2003) [Pubmed]
  30. Stimulation of the N-methyl-D-aspartate receptor promotes the biochemical differentiation of cerebellar granule neurons and not astrocytes. Moran, J., Patel, A.J. Brain Res. (1989) [Pubmed]
  31. Effects of protein kinase C modulation on NMDA receptor mediated regulation of neurotransmitter enzyme and c-fos protein in cultured neurons. Patel, A.J., Hunt, A., Jacques-Berg, W., Kiss, J., Rodriguez, J. Neurochem. Res. (1995) [Pubmed]
  32. A simple animal model of hyperammonemia. Azorín, I., Miñana, M.D., Felipo, V., Grisolía, S. Hepatology (1989) [Pubmed]
  33. Glutamine metabolism in rat hepatocytes. Stimulation by a nonmetabolizable analog of leucine. Zaleski, J., Wilson, D.F., Erecinska, M. J. Biol. Chem. (1986) [Pubmed]
  34. Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase. Curthoys, N.P., Kuhlenschmidt, T. J. Biol. Chem. (1975) [Pubmed]
  35. In vitro characterization of the mitochondrial processing and the potential function of the 68-kDa subunit of renal glutaminase. Srinivasan, M., Kalousek, F., Curthoys, N.P. J. Biol. Chem. (1995) [Pubmed]
  36. Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase. Smith, E.M., Watford, M. J. Biol. Chem. (1990) [Pubmed]
  37. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Rouse, K., Nwokedi, E., Woodliff, J.E., Epstein, J., Klimberg, V.S. Ann. Surg. (1995) [Pubmed]
  38. The effects of administration of nitric oxide inhibitors during small bowel preservation and reperfusion. Mueller, A.R., Platz, K.P., Langrehr, J.M., Hoffman, R.A., Nussler, A.K., Nalesnik, M., Billiar, T.R., Schraut, W.H. Transplantation (1994) [Pubmed]
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